Early Tissue Effects of Stereotactic Body Radiotherapy in Spinal Metastases

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jasper G. Steverink, Stefan M. Willems, Marielle E.P. Philippens, Nicolien Kasperts, Wietse S.C. Eppinga, Anne L. Versteeg, Joanne M. van der Velden, Salman Faruqi, Arjun Sahgal, Jorrit-Jan Verlaan
IntroductionStereotactic body radiotherapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent literature suggests radio-biologic effects of SBRT expanding beyond the traditional concept of DNA-damage. Anti-tumor immunity, vascular damage leading to tumor necrosis and increased rates of tumor apoptosis are implied, yet in-human evidence remains scarce. This study reports unique pathologic confirmation of SBRT-induced biologic effects within spinal metastases treated with pre-operative SBRT.Materials and MethodsTen patients with spinal metastases secondary to various solid tumors were treated with pre-operative single-fraction SBRT (18 Gy) to the MRI-defined macroscopic metastasis followed by spinal stabilization within 24 hours. Perioperative samples of spinal metastases were obtained, and 6 patients also had a pre-SBRT biopsy for matched comparison. Samples were stained for tumor necrosis on routine HE slices and subsequently underwent immunohistochemical staining for T-cells (CD3+, CD4+, CD8+), NK-cells (CD56+), endothelium (CD31+) and apoptotic activity (Caspase-3).ResultsPerioperative biopsies were obtained approximately 6 hours (range 4.5-7.5h) or 21 hours (range 18.5-22.5h) post-SBRT. Necrosis was observed in 83% of 21h post-SBRT samples (5/6), as compared to 0% in pre-SBRT biopsies (0/6) and 6h post-SBRT biopsies (0/4). Tumor cell apoptosis increased greatly in 21h post-SBRT samples compared to pre- and 6h post-SBRT. CD31+ vessel counts decreased post-SBRT as did mitotic activity. Notably, both of the renal cell metastases displayed major decreases in vessel density. Desmoplastic reaction was visible in 67% (4/6) with pre-SBRT samples compared to 100% (10/10) post-SBRT samples. T- and NK-cell counts were relatively unaffected.ConclusionHigh-dose single-fraction SBRT induced tumor necrosis, desmoplasia and tumor apoptosis and decreased tumor vessel density within 24 hours, even in renal cell metastases. The role of immune cells seems limited in this early phase. These first-in-man results imply direct vascular- and DNA-damage mechanisms important in the clinical efficacy specific to spine SBRT.



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